Koagulacijski faktor VII

F7
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4YT7, 1BF9, 1CVW, 1DAN, 1DVA, 1F7E, 1F7M, 1FAK, 1FF7, 1FFM, 1J9C, 1JBU, 1KLI, 1KLJ, 1O5D, 1QFK, 1W0Y, 1W2K, 1W7X, 1W8B, 1WQV, 1WSS, 1WTG, 1WUN, 1WV7, 1YGC, 1Z6J, 2A2Q, 2AEI, 2AER, 2B7D, 2B8O, 2BZ6, 2C4F, 2EC9, 2F9B, 2FIR, 2FLB, 2FLR, 2PUQ, 2ZP0, 2ZWL, 2ZZU, 3ELA, 3TH2, 3TH3, 3TH4, 4IBL, 4ISH, 4ISI, 4JYU, 4JYV, 4JZD, 4JZE, 4JZF, 4NA9, 4NG9, 4NGA, 4X8S, 4X8T, 4X8U, 4X8V, 4YT6, 4ZXX, 4ZXY, 4Z6A, 4ZMA, 4YLQ, 5I46
Identifikatori
Aliasi	F7
Vanjski ID-jevi	OMIM: 613878 MGI: 109325 HomoloGene: 7710 GeneCards: F7
Lokacija gena (čovjek)
Hrom.	Hromosom 13 (čovjek)
Kraj	113,120,685 bp
Lokacija gena (miš)
Hrom.	Hromosom 8 (miš)
Kraj	13,085,809 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • endopeptidase activity; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • serine-type peptidase activity; • hydrolase activity; • serine-type endopeptidase activity; • signaling receptor binding;
Ćelijska komponenta	• Vezikula; • endoplasmic reticulum lumen; • ćelijska membrana; • extracellular region; • Golgi lumen; • Vanćelijsko; • serine-type peptidase complex; • collagen-containing extracellular matrix;
Biološki proces	• Hemostaza; • positive regulation of protein kinase B signaling; • GO:1904578 response to organic cyclic compound; • positive regulation of cell migration; • positive regulation of platelet-derived growth factor receptor signaling pathway; • Proteoliza; • response to estrogen; • positive regulation of leukocyte chemotaxis; • endoplasmic reticulum to Golgi vesicle-mediated transport; • response to vitamin K; • positive regulation of blood coagulation; • response to nutrient levels; • animal organ regeneration; • response to growth hormone; • response to hormone; • blood coagulation, extrinsic pathway; • positive regulation of positive chemotaxis; • response to thyroid hormone; • protein processing; • Koagulacija (krv); • response to 2,3,7,8-tetrachlorodibenzodioxine; • response to estradiol; • response to carbon dioxide; • response to genistein; • response to cholesterol; • Jednodnevni biološki ritam; • response to thyroxine; • response to Thyroid stimulating hormone; • response to hypoxia; • response to anticoagulant; • response to astaxanthin; • response to thyrotropin-releasing hormone;
	Izvori:Amigo / QuickGO
Ortolozi
	2155
	14068
	ENSG00000057593
	ENSMUSG00000031443
	P08709
	P70375
	NM_000131; NM_001267554; NM_019616
	NM_010172
	NP_000122; NP_001254483; NP_062562
	NP_034302
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Koagulacijski faktor VII (EC 3.4.21.21, ranije poznat kao prokonvertin) jedan je od proteina koji uzrokuje zgrušavanje krvi u kaskadi zgrušavanja, a kod ljudi je kodiran genom F7, sa hromosoma 13. To je enzim klase serin-proteaza. Jednom kada se veže za tkivni faktor koji se oslobađa iz oštećenih tkiva, pretvara se u faktor VIIa (ili faktor zgrušavanja krvi VIIa, aktivirani faktor zgrušavanja krvi VII), koji zauzvrat aktivira faktor IX i faktor X.

Korištenje genetičke rekombinacije rekombinantnog faktora VIIa (eptakog alfa) (trgovački nazivi uključuju NovoSeven) je odobrila FDA za kontrolu krvarenja kod hemofilija.^[5] Ponekad se neovlašteno koristi u teškim nekontroliranim krvarenjima, iako postoje sigurnosni problemi. Biosličnosni oblik rekombinantnog aktiviranog faktora VII (AryoSeven) je takođe dostupan, ali nema značajnu ulogu na tržištu.

U aprilu 2020. godine, američka FDA je odobrila novi rFVIIa proizvod, eptakog beta (SEVENFACT), prvi zaobilazeći agens (BPA) odobren u više od 2 decenije. Kao proizvod rFVIIa, eptakog beta djeluje u kompleksu sa tkivnim faktorom kako bi aktivirao faktor X do Xa, čime zaobilazi FVIII i FIX. Aktivacija faktora X u Xa pokreće zajednički put kaskade koagulacije, što dovodi do stvaranja ugruška na mjestu krvarenja. Aktivirani FVII vezuje se za endotelni protein C receptor (EPCR), što pojačava hemostazu . Jedna studija je pokazala da se eptakog beta veže za EPCR sa 25% do 30% većim afinitetom od eptakog alfa, istiskujući protein C sa EPCR vezivnih mjesta i smanjujući aktivaciju proteina, što doprinosi njegovom hemostatskom učinku.

Fiziologija

Glavna uloga faktora VII (FVII) je da pokrene proces koagulacije u sprezi sa tkivnim faktorom (TF/faktorom III). Tkivni faktor se nalazi na vanjskoj strani krvnih sudova – obično nije izložen krvotoku. Prilikom povrede krvnog suda, tkivni faktor je izložen krvi i cirkulirajućem faktoru VII. Jednom vezan za TF, FVII se aktivira na FVIIa pomoću različitih proteaza, među kojima su trombin (faktor IIa), faktor Xa, IXa, XIIa i sam FVIIa-TF kompleks. Kompleks faktora VIIa sa TF katalizuje konverziju faktora IX i faktora X u aktivne proteaze, odnosno faktora IXa i faktora Xa.^[6]

Djelovanje faktora ometa inhibitor puteva tkivnog faktora (TFPI), koji se oslobađa skoro odmah nakon iniciranja koagulacije. Faktor VII, koji je otkriven oko 1950. godine, zavisi od vitamina K i proizvodi se u jetri. Upotreba varfarina ili sličnih antikoagulansa smanjuje sintezu FVII u jetri.

Struktura

Aminokiselinska sekvenca

Dužina polipeptidnog lanca proteina je 466 aminokiselina, a molekulska težina je 51 594 molekulska masa — 51 594 Da

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MVSQALRLLC	LLLGLQGCLA	AGGVAKASGG	ETRDMPWKPG	PHRVFVTQEE
AHGVLHRRRR	ANAFLEELRP	GSLERECKEE	QCSFEEAREI	FKDAERTKLF
WISYSDGDQC	ASSPCQNGGS	CKDQLQSYIC	FCLPAFEGRN	CETHKDDQLI
CVNENGGCEQ	YCSDHTGTKR	SCRCHEGYSL	LADGVSCTPT	VEYPCGKIPI
LEKRNASKPQ	GRIVGGKVCP	KGECPWQVLL	LVNGAQLCGG	TLINTIWVVS
AAHCFDKIKN	WRNLIAVLGE	HDLSEHDGDE	QSRRVAQVII	PSTYVPGTTN
HDIALLRLHQ	PVVLTDHVVP	LCLPERTFSE	RTLAFVRFSL	VSGWGQLLDR
GATALELMVL	NVPRLMTQDC	LQQSRKVGDS	PNITEYMFCA	GYSDGSKDSC
KGDSGGPHAT	HYRGTWYLTG	IVSWGQGCAT	VGHFGVYTRV	SQYIEWLQKL
MRSEPRPGVL	LRAPFP

Faktor VII dijeli zajedničku arhitekturu domena sa faktorima IX i X.

Genetika

Gen za faktor VII nalazi se na hromosomu 13 (sekvenca 13q34).

Uloga u bolesti

Nedostatak faktora VII (kongenitalni nedostatak prokonvertina) je rijedak i nasljeđuje se recesivno. Predstavlja se kao poremećaj krvarenja sličan hemofiliji. Liječi se rekombinantnim faktorom VIIa (NovoSeven ili AryoSeven). Pristupi genske terapije u liječenju nedostatka FVII su vrlo obećavajući (^[7]).

Medicinska upotreba

Rekombinantni faktor VIIa, koji se prodaje pod trgovačkim nazivima AryoSeven i NovoSeven, koristi se za osobe sa hemofilijom (sa nedostatkom faktorom VIII ili IX ) koji su razvili antitijela protiv zamjenskog faktora koagulacije.

Također se koristio i kod nekontrolisanog krvarenja,^[8]^[9] ali njegova uloga u ovom okruženju je kontroverzna s nedostatkom dokaza koji bi podržali njegovu upotrebu izvan kliničkih ispitivanja.^[10] Prvi izveštaj o njegovoj upotrebi kod krvarenja bio je kod izraelskih vojnika sa nekontrolisanim krvarenjem 1999.^[11] Rizici njegove upotrebe uključuju povećanje arterijske tromboze.^[10] Međutim, studije na životinjama nisu pokazale komplikacije kao kod ljudi; zapravo iste studije pokazuju bolju prognozu. U vojnim okruženjima koristi se kao izvanredna intervencija kod komplikacija povezanih s diseminiranom intravaskularnom koagulacijom krvarenja uzrokovanom penetrirajućom traumom.^[12]

Rekombinantni ljudski faktor VII, iako je u početku izgledao obećavajuće u unutarlobanjskom krvarenju, nije pokazao korist nakon daljnjih studija i ovo se više ne preporučuje.^[13]^[14]

Interakcije

Pokazalo se da faktor VII reaguje sa tkivnim faktorom i protein kinazom C.^[15]^[16]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000057593 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031443 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Biron-Andreani, C; Schved, JF (januar 2019). "Eptacog beta: a novel recombinant human factor VIIa for the treatment of hemophilia A and B with inhibitors". Expert Review of Hematology. 12 (1): 21–28. doi:10.1080/17474086.2019.1560259. PMID 30577721. S2CID 58538425.
^ Wajima T, Isbister GK, Duffull SB (septembar 2009). "A comprehensive model for the humoral coagulation network in humans". Clinical Pharmacology and Therapeutics. 86 (3): 290–8. doi:10.1038/clpt.2009.87. PMID 19516255. S2CID 205121835.
^ Marcos-Contreras OA, Smith SM, Bellinger DA, Raymer RA, Merricks E, Faella A, Pavani G, Zhou S, Nichols TC, High KA, Margaritis P (2016). "Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII". Blood. 127 (5): 565–71. doi:10.1182/blood-2015-09-671420. PMC 4742547. PMID 26702064.
^ Roberts HR, Monroe DM, White GC (decembar 2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood. 104 (13): 3858–64. doi:10.1182/blood-2004-06-2223. PMID 15328151.
^ "Uncontrolled Bleeding and Injury Lawsuit Claims". Arhivirano s originala, 16. 6. 2016. Pristupljeno 26. 8. 2015.
^ ^a ^b Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C (mart 2012). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia" (PDF). The Cochrane Database of Systematic Reviews. 3 (3): CD005011. doi:10.1002/14651858.CD005011.pub4. hdl:10871/13808. PMID 22419303.
^ Kenet G, Walden R, Eldad A, Martinowitz U (novembar 1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet. 354 (9193): 1879. doi:10.1016/S0140-6736(99)05155-7. PMID 10584732. S2CID 23159895.
^ Hodgetts, T. J.; Kirkman, E.; Mahoney, P. F.; Russell, R.; Thomas, R.; Midwinter, M. (1. 12. 2007). "UK Defence Medical Services Guidance for the Use of Recombinant Factor VIIA (RFVIIA) in the Deployed Military Setting". Journal of the Royal Army Medical Corps (jezik: engleski). 153 (4): 307–309. doi:10.1136/jramc-153-04-18. ISSN 0035-8665. PMID 18619169. S2CID 10776054.
^ Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (februar 2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine. 352 (8): 777–85. doi:10.1056/NEJMoa042991. PMID 15728810.
^ Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (maj 2008). "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine. 358 (20): 2127–37. doi:10.1056/NEJMoa0707534. hdl:10067/688040151162165141. PMID 18480205.
^ Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M (juni 2003). "Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor". European Journal of Biochemistry. 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. PMID 12787023.
^ Zhang E, St Charles R, Tulinsky A (februar 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". Journal of Molecular Biology. 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. PMID 9925787.

Dopunska litereatura

Broze GJ, Majerus PW (februar 1980). "Purification and properties of human coagulation factor VII". The Journal of Biological Chemistry. 255 (4): 1242–7. doi:10.1016/S0021-9258(19)86020-9. PMID 7354023.
Versteeg HH, Peppelenbosch MP, Spek CA (decembar 2001). "The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?". Thrombosis and Haemostasis. 86 (6): 1353–9. doi:10.1055/s-0037-1616734. PMID 11776298.
Golino P (maj 2002). "The inhibitors of the tissue factor:factor VII pathway". Thrombosis Research. 106 (3): V257-65. doi:10.1016/S0049-3848(02)00079-8. PMID 12356487.

Vanjski linkovi

Official website
The MEROPS online database for peptidases and their inhibitors: S01.215 Arhivirano 29. 5. 2020. na Wayback Machine
CHES - Comprehensive Health Education Services LLC - Factor VII treatment and awareness [1]

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000057593 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031443 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[ERH-5] Biron-Andreani, C; Schved, JF (januar 2019). "Eptacog beta: a novel recombinant human factor VIIa for the treatment of hemophilia A and B with inhibitors". Expert Review of Hematology. 12 (1): 21–28. doi:10.1080/17474086.2019.1560259. PMID 30577721. S2CID 58538425.

[6] Wajima T, Isbister GK, Duffull SB (septembar 2009). "A comprehensive model for the humoral coagulation network in humans". Clinical Pharmacology and Therapeutics. 86 (3): 290–8. doi:10.1038/clpt.2009.87. PMID 19516255. S2CID 205121835.

[7] Marcos-Contreras OA, Smith SM, Bellinger DA, Raymer RA, Merricks E, Faella A, Pavani G, Zhou S, Nichols TC, High KA, Margaritis P (2016). "Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII". Blood. 127 (5): 565–71. doi:10.1182/blood-2015-09-671420. PMC 4742547. PMID 26702064.

[8] Roberts HR, Monroe DM, White GC (decembar 2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood. 104 (13): 3858–64. doi:10.1182/blood-2004-06-2223. PMID 15328151.

[9] "Uncontrolled Bleeding and Injury Lawsuit Claims". Arhivirano s originala, 16. 6. 2016. Pristupljeno 26. 8. 2015.

[Cochrane2012-10] Simpson E, Lin Y, Stanworth S, Birchall J, Doree C, Hyde C (mart 2012). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia" (PDF). The Cochrane Database of Systematic Reviews. 3 (3): CD005011. doi:10.1002/14651858.CD005011.pub4. hdl:10871/13808. PMID 22419303.

[11] Kenet G, Walden R, Eldad A, Martinowitz U (novembar 1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet. 354 (9193): 1879. doi:10.1016/S0140-6736(99)05155-7. PMID 10584732. S2CID 23159895.

[12] Hodgetts, T. J.; Kirkman, E.; Mahoney, P. F.; Russell, R.; Thomas, R.; Midwinter, M. (1. 12. 2007). "UK Defence Medical Services Guidance for the Use of Recombinant Factor VIIA (RFVIIA) in the Deployed Military Setting". Journal of the Royal Army Medical Corps (jezik: engleski). 153 (4): 307–309. doi:10.1136/jramc-153-04-18. ISSN 0035-8665. PMID 18619169. S2CID 10776054.

[13] Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (februar 2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine. 352 (8): 777–85. doi:10.1056/NEJMoa042991. PMID 15728810.

[14] Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T (maj 2008). "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage". The New England Journal of Medicine. 358 (20): 2127–37. doi:10.1056/NEJMoa0707534. hdl:10067/688040151162165141. PMID 18480205.

[pmid12787023-15] Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M (juni 2003). "Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor". European Journal of Biochemistry. 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. PMID 12787023.

[pmid9925787-16] Zhang E, St Charles R, Tulinsky A (februar 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". Journal of Molecular Biology. 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. PMID 9925787.

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